Immuno: Malabsorption CPC Flashcards
List three causes of microcytic anaemia.
- Iron deficiency
- Thalassaemia trait
- Anaemia of a chronic disease
Iron studies to differentiate microcytic anaemia
What is anisopoikilocytosis and which type of anaemia is it associated with?
- Variations in size and shape of cells
- Associated with iron deficiency anaemia (and thalassaemia trait to a lesser degree)
What is basophilic stippling? List some causes.
- Basophilic appearance of red blood cells caused by the presence of aggregated ribosomal material
Causes:
beta-thalassaemia trait
lead poisoning
alcoholism
sideroblastic anaemia
Which condition do hypersegmented neutrophils tend to be present in?
Megaloblastic anaemia - due to impaired DNA synthesis
List some causes of megaloblastic anaemia.
- B12 deficiency
- Folate deficiency
- Drugs
In which conditions might you see target cells (codocytes)?
- Iron deficiency
- Thalassaemia
- Hyposplenism
- Liver disease
NOTE: target cells have a high SA: V ratio
What are Howell-Jolly bodies? Which condition are they associated with?
- Nuclear remnants present within red blood cells
- Present in hyposplenism, as these remnants are normally removed by the spleen
List some causes of iron deficiency.
- Blood loss (major cause)
- Poor diet
- Malabsorption
- Combinations of the above
iron deficiency anemia blood film features
hypochromic, microcytic
anisopoikilocytosis
megaloblastic anaemia blood film features
hypersegmented neutrophils
macrocytes
hyposplenism blood film features
Target cells
Howell jolly bodies
List some causes of B12 and folate deficiency.
- Poor diet
- Malabsorption
- Pernicious anaemia
List some causes of hyposplenism.
Absent spleen:
* therapeutic
* trauma
Poorly-functioning spleen:
* inflammatory bowel disease
* Coeliac disease
* sickle cell disease
* SLE
Which deficienceies are typically seen in Coeliac disease?
- Iron
- B12
- Folate
- Fat
- Calcium
Which deficiencies are typically seen in Crohn’s disease?
- B12
- Bile salts
Which deficiencies are typically seen in pancreatic disease?
- Fat
- Calcium
- B12
Which investigatio are typically performed in Coeliac disease?
- CRP, ESR, Faecal elastase
- Serological tests
- Upper GI endoscopy and distal duodenal biopsy (GOLD STANDARD)
Which gene locus does the heritability of coeliac disease tend to frequently map to?
MHC complex gene loci
Which HLA alleles are particularly common in patients with coeliac disease?
- HLA-DQ2 (80%) - DQA1*0501 and DQB1*02 alleles
- HLA-DQ8
polygenic autoimmune
Describe the T cell response to gluten in coeliac disease.
- Peptides from gluten (gliadin) are deamidated by tissue transglutaminase
- Deamidated gliadin is taken up by antigen-presenting cells and presented via HLA molecules to CD4+ T cells
- CD4+ T cell activation results in secretion of IFN-gamma and may increase IL-15 secretion
- These cytokines promote activation of intra-epithelial lymphocytes (gamma-delta T cells)
- The intraepithelial lymphocytes will kill epithelial cells via the NKG2D receptor (normally recognises the stress protein MICA)
Describe the B cell response to gluten in coeliac disease.
- B cells will process gluten antigens and present it via HLA molecules to CD4+ T cells
- The primed T cells will provide help to the B cells via CD40L: CD20 to allow B cells to undergo germinal centre reactions
- B cells undergo isotype switching and affinity maturation to become memory cells and plasma cells which produce antibodies against gliadin
Which auto-antibodies may be tested when investigating coeliac disease?
anti TTG (most specific) and anti EMA
(antibodies against deaminated gliadin peptide is an old + non specifc test)
if +ve –> do an endoscopy + duodenal biopsy to confirm diagnosis
What important test should be performed before checking anti-tTG and anti-endomysial antibody levels?
- IgA levels
- IgA deficiency can produce false-negative results
What are the characteristic histological features of coeliac disease?
- villous atrophy with crypt hyperplasia
- Intra-epithelial lymphocytes
Needs to correlate with serology + clinical findings –> there are other potential causes of these results
from duodenal biopsy
Describe the villous atrophy seen in coeliac disease.
- Normal villous: crypt ratio is about 2-4: 1
- In coeliac disease, villous height is reduced and crypts become hyperplastic
- This leads to a reduced or reversed villous: crypt ratio
- The mucosa remains the same thickness due to crypt hyperplasia
- However, decreased surface area (due to villous atrophy) leads to malabsorption
List some other causes of villous atrophy.
- Giardiasis
- Tropical sprue
- Crohn’s disease
- Drugs - statins
- Radiation/chemotherapy
- Nutritional deficiencies
- Graft-versus-host disease
- Microvillous inclusion disease
- Common variable immunodeficiency
How many intraepithelial lymphocytes would you expect to see in coeliac disease?
More than 20 IELs/100 epithelial cells
NOTE: normal would be < 20
they are CD8+ –> confirm with CD3 staining
List some other causes of high intraepithelial lymphocytes.
- Dematitis herpetiformis
- Giardiasis
- Cows’ milk protein sensitivity
- IgA deficiency
- Tropical sprue
- Post-infective malabsorption
- Drugs (NSAIDs)
- Lymphoma
What does the interpretation of the histological report in suspected coeliac disease depend on?
Dietary history (e.g. if the patient has been avoiding gluten then they may have normal histology)
How is coeliac disease managed?
Strict adherence to a gluten-free diet
* gluten is in wheat, barley, rye and some oats
List some complications of coeliac disease.
- Malabsorption
- Osteomalacia and osteoporosis
- Neurological disease (epilepsy and cerebral calcification)
- Lymphoma (causes multi-focal T cell lymphoma)
- Hyposplenism
What does a high anti-tTG antibody level in a patient with previously diagnosed coeliac disease suggest?
Poor compliance with the diet
Complications (e.g. lymphoma)
How often should a DEXA scan be performed in coeliac patients?
Every 3-5 years
What does mortality in untreated coeliac disease tend to be due to?
- Malignancy (lymphoma)
- Infection
List some conditions that are frequently associated with coeliac disease.
- Dermatitis herptiformis
- Type 1 diabetes mellitus
- Autoimmune thyroid disease
- Down syndrome
- SLE
- Autoimmune hepatitis
